The aim of the proposed research is to obtain an understanding of two broad phenomena: 1) the role of phospholipids, especially the polar head group, in membrane structure and function, and 2) the mechanisms that regulate phospholipid synthesis in relation to macromolecular synthesis and cell growth. Methods have been developed to manipulate the lipid composition of LM cell with respect to the acyl group and the polar head group of the phospholipids. Subcellular membrane fractions will be isolated from cells with different lipid compositions and correlations will be made with the physical and biochemical properties of the membranes. Physical properties of the membranes will be studied by fluorescent techniques and a number of lipid-requiring enzymes will be studied to determine the effect of altering the phospholipid composition on their activity. Another aspect of this work will utilize genetic and biochemical methods to study the relationship between the glycerol-3-phosphate acyltransferase and adenylate kinase. This study will test the hypothesis that when the rate of phospholipid syntheses is altered by changing the activity of the acyltransferase, the activity of adenylate kinase is also changed. This in turn, regulates the rate of macromolecular synthesis and cell growth. Bibliographic references: Ferguson, K. A., Glaser, M. and Vagelos, P.R. (1975) "Alteration of Fatty Acid Composition of LM Cells by Lipid Supplementation and Temperature" Biochemistry 14, 146-151. Glaser, M., Ferguson, K.A. and Vagelos, P.R. (1974) "Manipulation of the Phospholipid Composition of Tissue Culture Cells" Proc. Nat. Acad. Sci. USA 71, 4072-4076.